Pentosan polysulfate (PPS), a semi-synthetic polyanion, has been under investigation here for a number of years as a prophylactic treatment for migraine and cluster headache. Since we observed an increase of circulating T-cells in treated patients and because of the reported synergism of another sulfated polyanion, dextran sulfate, with AZT, we have performed in-vitro experiments to evaluate the therapeutic potential of this drug. Using human peripheral blood mononuclear cells we have been able to demonstrate synergism of PPS with aziduvine (AZT) in the suppression of HIV-1 growth. We also observed that PPS and dextran sulfate alone in concentrations less than 1.Omug/ml stimulated viral replication. This latter finding is particularly important because of the reported "underground market" for dextran sulfate. It suggests that persons with AIDS could actually worsen their condition if they were to take polyanions such as dextran. On the other hand, the finding of a powerful synergism between AZT and PPS gives encouragement to careful design of clinical research to evaluate this substance as an adjunct to the treatment of AIDS that might permit effective lower dosing of AZT.